A simple and reliable bile acid assay in human serum by LC‐MS/MS

BackgroundBile acids, as important signaling molecules and regulatory factors acting on glucose, lipid, and energy metabolism, are always involved in liver, biliary, and intestinal diseases. Development and validation of a simple liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method for determination of bile acids is significant for the routine clinical testing.MethodsFifty microlitre of serum was mixed with 10 μl of the internal standard working solution and then 140 μl of methanol for protein precipitation. After centrifuged, the supernatant was directly used for LC‐MS/MS analysis.ResultsGood separation of all bile acid species was achieved. The method was validated with consistent linearity for individual bile acids, good recovery, low carryover, satisfactory sample stability, and analytical specificity against hemolysis, lipemia, and bilirubinemia. The intra‐day and the inter‐day imprecision values were in the range of 1.53%–10.63% and 3.01%–13.98%, respectively. No obvious matrix effect was observed. The reference intervals of bile acids in adults have been established for the clinical testing.ConclusionsThe low sample volume, simple sample preparation, good separation of all species, and satisfying validation results make this LC‐MS/MS approach suitable for usage as a high‐throughput assay in routine clinical laboratories.     

基于人为因素分析及分类系统的放射治疗安全事件人为因素分析及事故链探究

目的 分析放射治疗安全事件中的人为因素并确定这些人为因素之间的关系,寻找放疗安全事件的潜在事故链。方法 基于放射肿瘤事件学习系统纳入60例放疗安全事件,利用人为因素分析及分类系统(HFACS)进行致因识别及频率统计分析,基于分析结果采用潜在类别分析(LCA)方法对事故致因的关联性进行研究。结果 计划设计阶段的错误是最常见的事件类型,占比35%,组织氛围、监督不充分以及人员因素分别是HFACS各个层级中最主要的事件致因,其频率指数分别为4.66%、15.68%和16.20%。LCA分析确定了3条常见放疗事故链,其中两条事故链起源于组织氛围问题,一条事故链起源于组织过程问题,并通过不同的人为因素"漏洞"向下传递。结论 HFACS可帮助溯源导致放射治疗安全事件的各层级人为因素,本研究发现了放疗安全事件的高频致因和3条事故链,可为建立针对性的安全防御措施提供指导。     

Rational Design of Waterborne Polyurethane Pressure Sensitive Adhesives for Different Working Temperatures

The appropriate pressure sensitive adhesion performances at working temperature are vital for the applications of waterborne polyurethane (WPU). Understanding the relationship among rheological behaviors, macromolecular structures and adhesive performances can be very useful to the rational design of waterborne polyurethane pressure sensitive adhesives (WPU-PSAs) for different operating temperatures, as well as other kinds of adhesives. In this study, four kinds of WPU-PSAs were prepared by reacting polypropylene glycol (PPG), hydrogenated hydroxyl-terminated polybutadiene (HHTPB), dimethyl alcohol propionic acid (DMPA), 1,6-hexamethylene diisocyanate (HDI) and four kinds of chain extenders. Gel permeation chromatography (GPC), swelling and rheology tests were used in parallel with an analysis of adhesive performances of the dried films of the adhesives. Results showed that, in addition to the nature of chain extenders playing a role on the rheological behaviors and adhesive performances of polymer, the gel content could be used to adjust the macromolecular structure and molecular weight distribution of polymer, thus distinctly affected the adhesive performances of PSA. The relationship among rheological behaviors, macromolecular structure and adhesive performances was investigated, and the rational design of WPU was achieved with appropriate pressure sensitive adhesion properties for different working temperatures of 25 and 60 °C.     

STAT3 as a target for sensitizing prostate cancer cells to irradiation

Radioresistance of prostate cancer (PCa) is a major factor leading to local failure of radiotherapy. STAT3 is an oncogenic protein that was recently found to be activated in PCa tumors. This study aimed to investigate the radiosensitization effect of targeting STAT3 in PCa tumors. Here, the radiosensitization effect of STAT3 blockade was investigated by clonogenic assay, flow cytometry and western blot analysis in human PCa cells in vitro and in vivo. We demonstrated that STAT3 blockade with a STAT3 inhibitor or siRNA increased the radiosensitivity of PCa cells and that radiation together with STAT3 blockade induced more apoptosis and double-strand breaks (DSBs) than radiation alone in LNCaP cells. In addition, radiation induced STAT3 activation and survivin expression in PCa cells, which was inhibited by STAT3 blockade. Transfection with survivin cDNA attenuated the radiosensitization effect of STAT3 blockade. These effects were further confirmed by in vivo studies, which showed that the STAT3 inhibitor enhanced the treatment efficacy of radiation on LNCaP xenografts with decreased STAT3 activation and survivin expression.These findings suggest that STAT3 blockade radiosensitizes PCa cells through regulation of survivin. Thus, our study has revealed STAT3 as a potential sensitizer for irradiation in PCa cells. Its clinical application as an adjuvant in radiotherapy of PCa should be explored in the future.     

Superior Radiation Resistance of ZrO2-Modified W Composites

The microstructure and mechanical properties of pure W, sintered and swaged W-1.5ZrO₂ composites after 1.5 × 10¹⁵ Au⁺/cm² radiation at room temperature were characterized to investigate the impact of the ZrO₂ phase on the irradiation resistance mechanism of tungsten materials. It can be concluded that the ZrO₂ phase near the surface consists of two irradiation damage layers, including an amorphous layer and polycrystallization regions after radiation. With the addition of the ZrO₂ phase, the total density and average size of dislocation loops, obviously, decrease, attributed to the reason that many more glissile 1/2<111> loops migrate to annihilate preferentially at precipitate interfaces with a higher sink strength of 7.8 × 10¹⁴ m⁻²_. The swaged W-1.5ZrO₂ alloys have a high enough density of precipitate interfaces and grain boundaries to absorb large numbers of irradiated dislocations. This leads to the smallest irradiation hardening change in hardness of 4.52 Gpa, which is far superior to pure W materials. This work has a collection of experiments and conclusions that are of crucial importance to the materials and nuclear communities.     

苯磺酸氨氯地平与氯沙坦治疗原发性高血压的疗效分析

目的:研究苯磺酸氨氯地平与氯沙坦治疗原发性高血压的临床效果.方法:将2015年1月～2017年3月于我院接受治疗的原发性高血压患者100例作为研究对象,按照治疗方法分为对照组和试验组.对照组采用卡托普利联合吲哚帕胺治疗,试验组采用苯磺酸氨氯地平联合氯沙坦治疗.比较两组治疗效果,并对两组不良反应发生情况进行比较.结果:试验组治疗总有效率较对照组明显更高,两组数据相比P<0.05.试验组不良反应发生率明显低于对照组,两组数据相比P<0.05.结论:苯磺酸氨氯地平联合氯沙坦治疗原发性高血压的临床效果显著,具有较高临床价值.     

Membrane Loaded Copper Oleate PEGylated Liposome Combined with Disulfiram for Improving Synergistic Antitumor Effect <Emphasis Type="BoldItalic">In Vivo</Emphasis>

Purpose

This work aims to create a novel Cu²⁺ liposome with excellent loading stability and develop synergistic effect with disulfiram (DSF) for the treatment of tumor.

Methods

Copper oleate was incorporated into the liposome membrane via alcohol injection method in this work. In vitro release test was applied to evaluate the release profile of the liposomes. Pharmacokinetic studies were performed in rats and the antitumor efficacy was assessed in mice bearing hepatoma xenografts.

Results

The copper oleate liposome (Cu(OI)₂-L) was formulated and the loading efficiency were more than 85%. TEM images confirmed that the Cu(OI)₂-L had a spherical morphology with an average diameter of 100 nm. Cu(OI)₂-L displayed a biphasic release profile, with >70% retained drug over 8 h incubation in PBS at pH 7.4. Pharmacokinetic studies demonstrated that Cu(OI)₂-L had a prolonged circulation time and increased AUC when compared to the injection of copper oleate solution. The antitumor efficacy test demonstrated an enhanced tumor inhibition rate with the treatment of Cu(OI)₂-L and DSF nanoparticles, indicating an improved synergistic antitumor effect.

Conclusions

The Cu(OI)₂-L was suitable to be employed in combination with disulfiram for tumor treatment and can also open up opportunities for targeted delivery of copper.